PMID- 36860170 OWN - NLM STAT- MEDLINE DCOM- 20230418 LR - 20230423 IS - 2162-3279 (Electronic) VI - 13 IP - 4 DP - 2023 Apr TI - Contactin-6-deficient male mice exhibit the abnormal function of the accessory olfactory system and impaired reproductive behavior. PG - e2893 LID - 10.1002/brb3.2893 [doi] LID - e2893 AB - INTRODUCTION: Contactin-6 (CNTN6), also known as NB-3, is a neural recognition molecule and a member of the contactin subgroup of the immunoglobulin superfamily. Gene encoding CNTN6 is expressed in many regions of the neural system, including the accessory olfactory bulb (AOB) in mice. We aim to determine the effect of CNTN6 deficiency on the function of the accessory olfactory system (AOS). METHODS: We examined the effect of CNTN6 deficiency on the reproductive behavior of male mice through behavioral experiments such as urine sniffing and mate preference tests. Staining and electron microscopy were used to observe the gross structure and the circuitry activity of the AOS. RESULTS: Cntn6 is highly expressed in the vomeronasal organ (VNO) and the AOB, and sparsely expressed in the medial amygdala (MeA) and the medial preoptic area (MPOA), which receive direct and/or indirect projections from the AOB. Behavioral tests to examine reproductive function in mice, which is mostly controlled by the AOS, revealed that Cntn6(-/-) adult male mice showed less interest and reduced mating attempts toward estrous female mice in comparison with their Cntn6(+/+) littermates. Although Cntn6(-/-) adult male mice displayed no obvious changes in the gross structure of the VNO or AOB, we observed the increased activation of granule cells in the AOB and the lower activation of neurons in the MeA and the MPOA as compared with Cntn6(+/+) adult male mice. Moreover, there were an increased number of synapses between mitral cells and granule cells in the AOB of Cntn6(-/-) adult male mice as compared with wild-type controls. CONCLUSION: These results indicate that CNTN6 deficiency affects the reproductive behavior of male mice, suggesting that CNTN6 participated in normal function of the AOS and its ablation was involved in synapse formation between mitral and granule cells in the AOB, rather than affecting the gross structure of the AOS. CI - (c) 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC. FAU - Zhang, Wei AU - Zhang W AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. FAU - Huang, Huiling AU - Huang H AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. FAU - Gui, Ailing AU - Gui A AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. FAU - Mu, Di AU - Mu D AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. FAU - Zhao, Tian AU - Zhao T AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. FAU - Li, Hongtao AU - Li H AD - State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China. FAU - Watanabe, Kazutada AU - Watanabe K AD - Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Niigata, Japan. FAU - Xiao, Zhicheng AU - Xiao Z AD - The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China. AD - Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne, Australia. FAU - Ye, Haihong AU - Ye H AUID- ORCID: 0000-0001-7282-6280 AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. FAU - Xu, Yiliang AU - Xu Y AD - Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230301 PL - United States TA - Brain Behav JT - Brain and behavior JID - 101570837 RN - 0 (contactin 6 protein, mouse) RN - 0 (Cell Adhesion Molecules, Neuronal) SB - IM MH - Animals MH - Female MH - Male MH - Mice MH - Neurogenesis MH - Neurons/physiology MH - *Olfactory Bulb MH - Vomeronasal Organ/physiology MH - *Cell Adhesion Molecules, Neuronal/metabolism MH - *Sexual Behavior, Animal PMC - PMC10097056 OTO - NOTNLM OT - accessory olfactory system OT - contactin-6 OT - dendrodendritic synapse OT - reproductive behavior COIS- The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. EDAT- 2023/03/03 06:00 MHDA- 2023/04/14 06:42 PMCR- 2023/03/01 CRDT- 2023/03/02 01:53 PHST- 2022/12/21 00:00 [revised] PHST- 2022/05/07 00:00 [received] PHST- 2023/01/05 00:00 [accepted] PHST- 2023/04/14 06:42 [medline] PHST- 2023/03/03 06:00 [pubmed] PHST- 2023/03/02 01:53 [entrez] PHST- 2023/03/01 00:00 [pmc-release] AID - BRB32893 [pii] AID - 10.1002/brb3.2893 [doi] PST - ppublish SO - Brain Behav. 2023 Apr;13(4):e2893. doi: 10.1002/brb3.2893. Epub 2023 Mar 1.